The Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study is an interdisciplinary, community-based, prospective longitudinal epidemiologic study examining the influences of race and socioeconomic status (SES) on the development of age-related health disparities among socioeconomically diverse African Americans and whites in Baltimore. This study investigates whether health disparities develop or persist due to differences in SES, differences in race, or their interaction. This study is unique because it will assess over a 20-year period physical parameters as well as evaluate genetic, biologic, demographic, and psychosocial, parameters of African American and white participants in higher and lower SES strata. It also employs novel research tools, mobile medical research vehicles, in hopes of improving participation rates and retention among minority and poor urban research participants. The domains of the HANDLS study include: nutrition, cognition, biologic biomarkers, body composition and bone quality, neuroanatomy, nephrology, health and financial literacy, physical function and performance, sociodemographics, psychosocial, neighborhood environment and cardiovascular disease. Utilizing data from these study domains will facilitate researchers understanding of the driving factors behind persistent black-white health disparities in overall longevity, cardiovascular disease, and cognitive decline.